A new research by the Department of Biology of the Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, USP, performed dating of rocks from the Amazon region, indicating its geological age with precision. Such analyzes provide greater understanding about the formation of the region and its fauna. The work is written by Marcos César Bissaro Junior, who was guided by Professor Annie Schmaltz Hsiou. It is the first time that the absolute dating in these sedimentary layers is performed, which made it possible to discover the exact time in which fossilized animals lived in the region.

Marcos César Bissaro Júnior – Photo: Reproduction

The analysis of these rocks from Talismã and Niterói sites, in the region between the states of Acre and Amazonas, revealed the phenomena that allowed a mega fauna to inhabit the region millions of years ago. These giant animals populated the marshy region that is now called the Pebas system, and could be more than ten meters long, ranging from reptiles to giant rodents. “We have seen that the diversity boom happened in the Neogene, the period where the Miocene is,” Marcos said.

According to Annie, dating can help to understand the origin of Amazonian biodiversity, the impact of the emergence of the Andes, which would have reversed the course of the Amazon River some 23 million years ago. This fact caused an accumulation of water in the studied region, forming a mega swamp, propitious for the proliferation of a rich mega-sized fauna. “All the water arms that underwent this change flowed into the Pebas system, creating this great lake. That’s the story the sediments in that region tell us.”

One of the species of Purussaurus was described: P. brasiliensis (illustrative image), the largest of all, from Solimões Formation (Late Miocene, Acre) – Illustration: Ornitholestes via Wikimedia Commons/Public domain

This large lake most notably housed the largest crocodilians of the Cenozoic period in South America, Purussaurus brasiliensis, or Purussauro, which reached about 12 meters long. Another animal was Neopliblema, which would be a kind of giant capybara. These species, along with others like snakes, turtles and sloths, indicate, according to Annie, an environment extremely rich in water.

Annie Schmaltz Hsiou – Photo: Reproduction

The sediments analyzed date from the Miocene period, about 8 to 10 million years ago. The dates were made by measuring the presence of uranium and lead in the rocks. Uranium, which undergoes chemical decay, turns into lead over time. By measuring the amount of these elements in the minerals, it is possible to verify the age of the rocks.

Until the study, what was used to date the fossils was an estimate based on discoveries from other places in South America. According to the dating of these other fossils, there was attribution of the same estimated date to the discoveries in the Amazon. “A certain species lived in the Amazon, but it was also seen in the Miocene of Argentina, so it was assumed that they lived at the same time,” Annie explained.

“Now, with the absolute date, we can see not only when this Amazonian biome was formed, but also the fossils of the animals that lived in it.”

]]>Light might recover patients with severe traumatic brain injuryhttps://www5.usp.br/136519/light-might-recover-patients-with-severe-traumatic-brain-injury/
Mon, 20 May 2019 16:16:07 +0000https://www5.usp.br/?p=136519The therapy is based on the application of laser, emitted by diodes integrated into a helmet, to stimulate the recovery of injured brain tissue

Researchers at USP’s Medical School (FMUSP) have been developing a method to rehabilitate cognitive functions in patients with severe traumatic brain injury, victims of accidents or violence. The therapy is based on the application of laser, emitted by diodes integrated into a helmet, to promote the recovery of brain tissue.

Different therapies using light, gathered under the term photobiomodulation, have already been applied to various health problems – from orthopedic injuries and fibromyalgia to Alzheimer’s disease and depression –, any disease in which it is intended to promote or inhibit certain cellular functions, that is, to modulate these functions. In the case of trauma, the therapy is aimed at stimulating the regeneration of injured neurons.

Light-emitting diodes (LEDs) are able to penetrate the scalp and skull, and have the potential for improving the cellular activity of compromised brain tissue. Experiments have already been performed at other research centers to test LED therapy for head trauma, with promising results. Now, the researchers at FMUSP want to take a step further by developing different approaches to maximize the positive effects of this therapy and improve patients’ quality of life.

The neurosurgeon João Gustavo dos Santos – o: Researcher’s personal fileOne of the alternatives is to initiate therapy earlier, in the acute phase of the injury. To date, such therapy has been adopted only in patients’ recovery chronic phase, that is, months after the occurrence. Neurosurgeon João Gustavo R. P. dos Santos, researcher at FMUSP explained: “Our study is part of the first experiments using the technique, initiated by Margaret Naeser, in Boston. She has begun to treat mild trauma in the late stage, six months after the trauma, to try to improve the patients’ functionality, and had good results. Then, we thought of testing how it would be in the acute phase and in severe cases.”

Thus, the study will examine patients who suffer severe trauma and are hospitalized within 8 hours after the accident. “This hospital admission a few hours after the trauma reduces the occurrence of events that could confuse the results,” the doctor said.

In addition, patients included in the study should exhibit symptoms of diffuse axonal injury, which is damage to the axons of the neuron within the myelin sheath (see image), resulting in a severe degeneration of the white matter of the brain. This occurs because the axons, which constitute the white matter, are the transmission channels of nerve impulses between the neurons.

Diffuse axonal injury is related to events that cause acceleration and deceleration of the skull, that is, when there is abrupt interruption of the movement of the brain, as it happens in car accidents or falls from height. In severe trauma, which leads to unconsciousness and coma and that cannot be attributed either to hematomas (accumulation of blood in the brain or between the brain and skull), or to brain cancer, it is almost certain that there is diffuse axonal injury, which is difficult to treat. “Today, in the whole medicine, we still do not have any treatment for diffuse axonal injury, which is one of the pathologies associated with traumatic brain injury. Everything which is done is literally ‘to wait and see’ how it will progress, how the body will repair itself,” the researcher said.

Traumatic brain injury and the parts of the neuron – Images: Patrick J. Lynch via Wikimedia Commons and US National Institutes of Health. Patient receives transcranial LED therapy at Hospital das Clínicas – Photo: Provided by the researcher

The treatment proposed in the clinical trial establishes 18 sessions of LED stimulation at specific points of the skull for six weeks. The idea is that patients should be evaluated for their level of consciousness before the stimulation and also after one, three and six months from the first stimulation.

Transcranial LED therapy is expected to improve patients’ cognitive function as well as promoting beneficial changes in blood circulation.

Light That Heals

Light regenerative effect was discovered by chance in an experiment with mice that aimed to treat tumors. It was realized that the laser, in fact, promoted the healing of wounds in the rodents. When investigating why this happened, later studies have shown that, at the right intensity and time, light is able to increase the oxygenation of the mitochondria, the energy power plants in the cells, accelerating the process of tissue regeneration.

Double-blind, randomized, controlled trial

To increase the reliability level of the results, the experiment is done within the double-blind, randomized and controlled methodology.

Check out how it works in the infographic below.

Publications

The preparation of the clinical trial has already resulted in four scientific articles published by the group:

The Current Role of Non-invasive Treatments in Traumatic Brain Injury;

Effects of transcranial LED therapy on the cognitive rehabilitation for diffuse axonal injury due to severe acute traumatic brain injury: study protocol for a randomized controlled trial;

According to the recommendations of an international group directed at the publication of quality clinical trials, the Consort – Consolidated Standards of Reporting Trials, before any clinical trial is performed, it must be registered on the Clinical Trials website online platform. Following such quality guidelines, the researchers’ work is available on this link.

]]>Pollution in Manaus alters Amazonian ecosystem functioninghttps://www5.usp.br/136017/pollution-in-manaus-alters-amazonian-ecosystem-functioning/
Tue, 14 May 2019 17:56:12 +0000https://www5.usp.br/?p=136017Pollutants generate particles that alter the incidence of solar radiation, photosynthesis, and the process of rain formation
Gases emitted by sources of pollution in Manaus (in the photo above), such as nitrogen oxides (NOx), oxidize in the forest atmosphere, condense and give rise to secondary aerosols, which alter the incidence of sunlight and the process of rain formation – Photo: FAPESP Agency, via FAPEAM.

The impact of pollution emitted in Manaus City on the Amazon rainforest is revealed in international research with the participation of USP’s Institute of Physics (IFUSP). Manaus’ urban pollutants, carried by the wind, have substances that react with the composition of the Amazon atmosphere, giving rise to particles known as secondary aerosols. The measurements made in the study show that in the forest region there was increase of up to 400% in the production of secondary aerosols, which modify the incidence of the solar radiation on the forest, altering the rate of photosynthesis and the mechanisms of rain formation, among other effects. The research is described in an article published on the multidisciplinary science journal Nature Communications.

According to Professor Paulo Artaxo, from USP’s Institute of Physics (IFUSP), one of the authors of the article, the increased production of secondary aerosols in the forest is mainly caused by high emissions of nitrogen oxides (NOx) in Manaus. “The interaction of NOx with free radicals also produces high concentrations of ozone (O3), a strong phytotoxic pollutant, which affects the stomata of the leaves and reduces carbon absorption by the Amazon forest,” he added.

Professor Paulo Artaxo: increased production of secondary aerosols in the Amazon rainforest is mainly caused by high emissions of nitrogen oxides (NOx) in Manaus – Photo: Marcos Santos/USP images

The work is one of the results of the GoAmazon 2014/15 experiment, which brings together researchers from Brazil, the United States, and Germany, and is supported by São Paulo Research Foundation, (FAPESP), Fundação de Amparo à Pesquisa do Amazonas (FAPEAM ), U.S. Department of Energy (DOE), and Germany’s Max Planck Institute. Professor Henrique Barbosa, from IFUSP, who also signs the article, declared: “The aim is to understand how the changes promoted by man can affect the clean atmosphere of the Amazon region, one of the few continental regions that still have preindustrial situations.” “During the rainy season, there are no fires and the atmosphere is very clean, with no comparison to the major urban centers’ air.”

Professor Henrique Barbosa, from the IFUSP: the aim of the research is to understand how the changes promoted by man can affect the clean atmosphere of the Amazon region – Photo: Cecilia Bastos/USP images

According to Professor Barbosa, aerosols in the atmosphere can be primary or secondary. “Primaries aerosols are emitted as particles, such as dust, pollen and soot. Secondary aerosols are produced from gases that undergo chemical reactions in the atmosphere, condense and give rise to new particles, including volatile organic compounds (VOCs),” he reported. “In the Amazon, there are VOCs that are emitted by the vegetation in a natural way, such as isoprenes and terpenes. However, gases emitted by sources of pollution (NOx, for instance) oxidize in the atmosphere, condense and give rise to secondary aerosols.”

Earlier work from the GoAmazon 2014/15 experiment has shown the impact of very fine aerosol particles on the mechanisms of cloud formation and development. “The droplets that make up the clouds are formed by water vapor that is deposited in the aerosol particles suspended in the atmosphere,” Barbosa explained. “Studies have shown that Manaus’ pollution plume has high concentrations of ultrafine particles that greatly modify the properties of clouds. This new study was able to model the formation processes of these nanometric particles, and studies some of the effects of these particles on the ecosystem.”

In the Amazon, Manaus’ pollution, carried by the wind, caused increase of 60% to 200% in the production of aerosols, and in some cases it reached 400%. “The mechanisms responsible for this increase have been modeled and unveiled. The increase in the amount of aerosols produced by oxidizing anthropogenic (generated by human activity), besides modifying the clouds, also changes the way in which the solar radiation reaches the ground,” Artaxo said. “Higher level of aerosols spreads direct radiation and decreases the amount of energy available for plants to perform photosynthesis and absorb carbon. At the same time, there is increase in diffuse radiation, which penetrates more into the woods and favors photosynthesis, but this only occurs up to a certain level of aerosols.”

In high aerosol levels, the blockage of direct solar radiation is greater and harms photosynthesis performance by the forest, hampering carbon fixation, Professor Artaxo declared. “New studies will be developed to detail the effects of this large production of secondary aerosols,” he affirmed. “This will be done with airplane experiments in 2020, the Chemistry of the Atmosphere: Brazil Field Experiment (CAFE), and in measures that have been taken at the Amazon Tall Tower Observatory, a 320-meter tower in the middle of the forest.” All these experiments are supported by FAPESP thematic projects.

Emissions of pollutants from Manaus, carried by the wind to the Amazon rainforest, affect the production of aerosols and alter processes that are critical to the forest, including photosynthesis, process of cloud and rain production and development, among others.

The paper Urban pollution greatly enhances formation of natural aerosols over the Amazon rainforest is signed by 36 authors, and nine are Brazilians, namely: Paulo Artaxo, Henrique Barbosa, Joel and Rita Ynoue, from USP; Eliane Gomes Alves and Rodrigo Souza, from Universidade do Estado do Amazonas (UEA); Helber Gomes, from Universidade Federal de Alagoas (UFAL); Adan Medeiros, from UEA and National Institute for Amazonian Research (INPA), and Suzane S. de Sá, from Harvard University, USA. The article has free access on the journal Nature Communications.

]]>Early weaning of babies affects maternal brain chemistryhttps://www5.usp.br/135999/early-weaning-of-babies-affects-maternal-brain-chemistry/
Tue, 14 May 2019 17:07:59 +0000https://www5.usp.br/?p=135999During lactation, there is increase in protein levels that regulate eating behavior, sleep and stress, and early weaning may cause imbalances
Levels of orexin, neuromodulator connected to eating behavior, sleep and stress, increase during lactation. According as weaning process progresses, levels decrease up to normality at the end of the period… Scientists have found that early weaning affects this process – Photo: Cecília Bastos/USP Images

Much is already known about the benefits of breastfeeding for the offspring’s health. What is little discussed – perhaps due to the small number of pieces of research that addresses the subject – is how much females’ brains change when their babies begin the weaning process, and the repercussion of early weaning on their behavior.

A recent contribution to this understanding came from a doctoral thesis conducted with mice at USP’s Institute of Biomedical Sciences (ICB). Researchers have found that levels of orexin, neuromodulator connected to eating behavior, sleep and stress, increased during lactation. According as weaning process progressed, levels decreased up to normality at the end of the period.

In mice, the teeth begin to erupt on the 14th day of life. Weaning process begins on the 15th day – the babies already walk, see, hear and feed on solids – and ends on the 22nd day, when the offspring stop interacting with the mother.

When the researchers promoted early weaning and prevented the babies from keeping on breastfeeding, the females were, on the 22nd day, with the same levels of orexin they had on the 15th day. “Higher levels of orexin in the brain may lead to sleep disorders, such as insomnia, increased stress, and even depression, as response to this higher stress,” neuroscientist Giovanne Baroni Diniz, author of the study, affirmed. He explains that in narcolepsy (excessive drowsiness), the levels of this neuromodulator are very low.

The study was conducted at ICB’s Department of Anatomy, under Professor Jackson Cioni Bittencourt’s guidance. The findings were considered so relevant that the neuroscientist received an invitation to defend the thesis at Maastricht University, in the Netherlands, last December, under Professor Harry W. M. Steinbusch’s supervision, and obtained double degree doctorate.

Increase of levels of orexin when breastfeeding is justified because the female needs to be more attentive to protect the offspring, and this neuromodulator promotes exactly that – Photo: Cecília Bastos/USP Images

“In functional terms, the study brings new data by demonstrating the role of orexin in lactation and weaning, leading to neuronal alterations of great magnitude in the maternal brain,” the neuroscientist explained.

Increase of this neuromodulator during breastfeeding is justified because the female needs to be more attentive to protect the offspring, and the orexin promotes exactly that. In turn, in a virgin female, the number of neurons attached to the neuromodulator is similar to that of mice with babies at the end of weaning.

Experiments

In the laboratory, the scientists promoted the early weaning of babies at 15, 17, 19 and 21 days of life. Soon after, they analyzed their mothers’ brains, specifically the hypothalamus region, which is very important to lactation, and where the neurons connected to the orexin are found. They used the FOS protein as a marker, since it indicates to scientists that the neuron was active an hour or two before analysis. Thus, the researchers can be sure of which neuron was activated at the time of weaning.

When analyzing the animals’ brains, they observed high levels of orexin activated, in amount higher than that found in the control group (virgin female mice). The researcher emphasizes that, in the hypothalamus, orexin splits locally into two groups: on the lateral side, there are the neurons that act on eating and rewarding behavior; and in the medial region (in the center) are those neurons associated with attention (stress) and sleep. In the experiment, they realized that practically the majority of active orexin cells were in the medial region.

The video below shows the 3D reconstruction of the hypothalamus. In yellow, the orexin cells activated hours earlier in the medial region are highlighted.

The results of the study point to the need for doctors to pay close attention to mothers who stopped breastfeeding. “The doctor should be aware of alterations in the pattern of sleep, or emotional changes that persist for a long time, because this mother may not have returned to normality,” he explained.

Giovanne Diniz explained that there is much that is not known about the nervous system and the process of lactation and gestation. “It’s an area that has a lot of room for research development. Historically, in science, there was a tendency not to use female subjects. Many studies only look into males. Therefore, in terms of women’s health and understanding the women’s physiological mechanisms, people know less,” he affirmed.

MCH: Melanin concentrating hormone

At the beginning of the doctoral research, the neuroscientist Giovanne Diniz started from the analysis of scientific articles showing brain alterations during gestation and lactation. About 20 substances have been detected. Among them, he has found the melanin concentrating hormone (MCH). In humans, it acts as a neuromodulator, that is, it is produced by neurons to alter the functioning of other neurons.

List with brain substances that undergo alterations during lactation and weaning and which were studied by ICB’s research –Photo: Cecília Bastos/USP Images

Scientists hypothesized that MCH could be associated with lactation because a group of these neurons appears in the female mice’s hypothalamus at the end of lactation. The same does not occur in males, in pregnant rats, at the beginning of the period, or even after, when the babies are weaned. However, after several experiments, researchers have discovered that it is orexin – not MCH – that performs a more specific role in lactation and weaning.

Double degree

The thesis to be defended at ICB addresses MCH performance in the body, and specifically with regard to how it communicates with the other nervous system cells. Orexin, in turn, was the subject of the thesis defended at Maastricht University.
Giovanne Diniz said that the prerequisites to defend the thesis in the Netherlands were: to be the first author of three papers on such research, and Netherlands’ thesis papers not allowed to participate in USP’s study.

The neuroscientist wrote the thesis, sent it to a Maastricht’s evaluation committee, and the work was accepted.

The results of his research were so relevant that he was invited to defend the thesis in a Dutch university, thus obtaining double-degree – Photo: Cecília Bastos/ USP Images

And without having to take any course at the Dutch university, Giovanne Diniz received his doctoral degree from Maastricht University. As for the defense at ICB, it is expected to occur until the second half of this year. After that, Diniz will have double-degree doctorate: one from the Dutch university, and other from USP.

Valéria Dias – Jornal da USP

]]>Growth hormone blockade stimulates weight losshttps://www5.usp.br/135964/growth-hormone-blockade-stimulates-weight-loss/
Tue, 14 May 2019 14:30:23 +0000https://www5.usp.br/?p=135964Discovery of the Institute of Biomedical Sciences sets a precedent for studies on new treatments for obesity
Growth hormone (GH) is also responsible for activating a group of hypothalamic neurons called AgRP, which control food intake and energy expenditure – Photo: Marcos Santos/USP Images

Growth hormone (GH) is produced by the pituitary gland and is responsible for regulating height and bone growth. However, a discovery by USP’s Institute of Biomedical Sciences (ICB) may not only make this hormone to have its name altered, but also require updating of physiology didactic textbooks. It is due to the fact that scientists have found GH as also responsible for activating a group of hypothalamic neurons called AgRP, which control food intake and energy expenditure.

In the experiments with mice, because of food deprivation, the control group animals’ organisms underwent a series of metabolic and endocrine alterations to save energy. Animals without GH receptors in AgRP neurons did not enter this “economic mode” and thus have lost more weight and body fat.

These findings set a precedent for GH blockade to be therapeutically useful in treating obesity. “In the long term, our findings may stimulate further research into the development of compounds or drugs aimed to optimize weight loss,” it was explained by Professor José Donato Júnior, from the Department of Physiology and Biophysics, one of the authors of the study.

“We have found that over 90% AgRP neurons express GH receptors,” Donato Junior stated. Feeling hungry is a sensation that comes from signals emitted by the brain, which knows that the person has not eaten because of a signal that was sent to it by some hormone: GH is that signal.

GH is like a siren that the body activates and is heard by AgRP neurons, since they have receptors for this hormone. And GH, acting on these neurons, coordinates all bodily adaptations aimed at energy saving.”

The Professor explained that a paper published in the 1960s on Science Magazine had already shown that GH is highly secreted when we are in food deprivation. To act on body growth, GH secretion must have a pulsatile pattern, that is, it has to be secreted in pulses over time. With food deprivation, GH is secreted continuously, but this new pattern prevents the hormone from acting to stimulate growth. But, then, why does the body produce GH during food deprivation?

Researchers have found that GH, by activating AgRP neurons during food deprivation, stimulates the “economic mode” of the body by decreasing both the secretion of thyroid hormones and the metabolism – Photo: Marcos Santos/USP Images

This was a question that scientists could not explain so far. The study has provided answers to this questioning: ICB’s researchers have found that GH, by activating AgRP neurons during food deprivation, stimulates the “economic mode” of the organism by decreasing both the thyroid hormone secretion and the metabolism. “That’s why it’s so difficult to lose weight: the body adapts to the situation,” Donato Júnior said.

Economic mode

The researchers have created mice without GH receptor for these neurons. When these animals underwent food deprivation, T4 hormone fell slightly, but this decrease was much more pronounced in the control group.

In the case of testosterone, which helps produce muscles and give strength, the mice without GH receptor did not have this hormone decreased, unlike the other group. In turn, the control group animals, during food deprivation, underwent metabolic and endocrine changes to save energy and enter the “economic mode.”

It is the action of GH on AgRP neurons that coordinates these adaptations. The mice without GH receptor in these neurons lost weight because they did not conserve energy during food deprivation.

Matter of survival

Another group’s finding was regarding leptin, secreted by white adipose tissue. The levels of this protein in the control group animals decreased with food deprivation. But the levels of the protein stopped lowering in animals without GH receptor.

“Leptin is a very important hormone to regulate hunger and energy expenditure, and we have found that GH plays a similar role. The increase in GH and the decrease in leptin levels are signs that reach the hypothalamus, transmitting that the body is in food deprivation and should save energy to ensure survival,” the Professor explained. In other words, if one mechanism fails, the other assumes the task. Previous studies have shown that when the body begins to lose fat, the level of leptin decreases, and this decrease is a signal that is also transmitted to the AgRP neuron.

José Donato Júnior: “In the long term, our findings may stimulate further research into the development of compounds or drugs aimed to optimize weight loss” – Photo: Marcos Santos/USP Images

According to the Professor, the person may have numerous strategies to lose weight, but from the moment the organism realizes that it is losing weight, it will adapt. This is because it is more interested in preserving the survival of the body than eliminating the excess pounds. The organism always sees weight loss as negative, even if that weight loss would bring benefits.

“In nature, it is very rare to find an obese animal. Maybe that’s why, somehow, during evolution, the body simply started considering only weight loss. When it detects this, it turns on the alert for the body to adapt and save energy. And that alert is exactly the role of GH,” he declared.

]]>International Committee approves of Brazilian chip for the LHC acceleratorhttps://www5.usp.br/127000/international-committee-approves-of-brazilian-chip-for-the-lhc-accelerator/
Mon, 25 Mar 2019 14:01:14 +0000https://www5.usp.br/?p=127000Totally developed in Brazil, chip will be in particle detectors in the Alice experiment of the Large Hadron Collider.

The final production phase of the Sampa chip, developed in Brazil especially for the experiment called Alice (A Large Ion Collider Experiment, one of the four major experiments at the LHC – Large Hadron Collider), has been given the green light by an international committee of reviewers, made up of experts in microelectronics. The LHC is the world’s largest particle accelerator; and is located on the French-Swiss border. The Sampa prototype has been validated after submission of the results of the tests performed on the chip in different places: Brazil, Cern, Sweden, France, Russia, USA and Norway.

After that meeting, called Production Readiness Review, international reviewers issued a favorable opinion regarding the immediate production of the chip which will be used in the Alice experiment. That capped a five-year-long project headed by USP researchers from the Physics Institute (IF) and the Polytechnic School (Poli), which also relied on the participation of researchers from Unicamp, and whose funding was provided by the São Paulo Research Foundation (Fapesp). “The project is wholly Brazilian, and a Norwegian scientist was involved in one of its parts. The chip intellectual property is ours”, praises IF Professor Marcelo Gameiro Munhoz, stressing he will follow up on the manufacturing process assigned to TSMC, a Taiwan-based company.

The Sampa chip has been proven to meet the needs of Alice particle detectors in which it will be used, called TPC (Time Projection Chamber) and MCH (Muon Chamber). Upon completion of all tests, the next step is the industrial production of 88,000 units, most of which are meant to be used in the Alice experiment.

The utilization of Sampa will not be limited to basic research. Teams from the Physics Institute are developing detection devices ready to be integrated into the chip as soon as it has been produced. “They are gas-filled radiation detectors; and one of the projects is to use it in X-ray imaging”, Munhoz reveals, saying that another project measures thermal neutrons released from nuclear reactors. According to the scientist, the Star experiment of the RHIC accelerator, at the Brookhaven National Laboratory, in the USA, will be the first to use Sampa in a real experiment application. They have already installed some units to be tested this year; and are supposed to set up all chips they will use next year.

Speed in a compact size

The Sampa chip integrates 32 channels occupying an area of about 82 mm². Its compact size translates into savings of cost, space and power for Alice, in which 17,000 Sampa units will be installed in the TPC, a chamber that is 5 m long and has a diameter of 5 m; and 40,ooo units in the MCH, a device farther from the collisions than the TPC. The higher density of the Sampa channels occupying less space allows it to cover bigger areas and be faster than the current two-chip system, in which one receives analog signals while the other converts them into digital signals. The Sampa chip achieves both of those functions.

The LHC, the largest particle accelerator ever built in the world; lies in a tunnel 27 km in circumference. It is an international collaboration with open access to the 10,00o scientists from 100 countries working directly on the project and involved in four experiments: Alice, Atlas, CMS, LHCb. The equipment will be shut down in 2019 for the performance of upgrades of the four experiments, and will resume operation in 2021. Teams from many countries have jointly taken part in preparing the upgrade. The capacity to produce a high-complexity compact chip motivated the Alice coordinating team to choose the Brazilian team to develop the new front-end chip for the experiment. The Sampa project is coordinated by professors Wilhelmus Van Noije, from Poli, and Marcelo Gameiro Munhoz, from IF.

From the IF Communication Department

]]>Research center at USP moves towards the development of a mathematical theory of the brainhttps://www5.usp.br/126961/research-center-at-usp-moves-towards-the-development-of-a-mathematical-theory-of-the-brain/
Mon, 25 Mar 2019 12:00:17 +0000https://www5.usp.br/?p=126961The Research, Innovation and Dissemination Center for Neuromathematics (RIDC NeuroMat) has worked to develop the new mathematics needed to construct a Theory of the Brain accounting for the experimental data gathered by neuroscience research

The study of the brain is probably the most important research topic of our times. An evidence of this claim is the concomitant worldwide creation of brain initiatives, including the BRAIN Initiative (USA, 2013), Human Brain Project (Europe, 2013), Brain/MINDS (Japan, 2014) and China Brain (China, 2016). FAPESP’s decision in 2013 to create the Research, Innovation and Dissemination Center for Neuromathematics (RIDC NeuroMat) spearheaded this direction of study.

The distinctive feature of NeuroMat in comparison with other initiatives is its emphasis on the development of a new mathematical framework to address the challenges raised by contemporary neurobiology. This feature goes along with the criticism that the Nobel prize laureate Edvard Moser raised against the Human Brain Project, which applies to other initiatives as well: “As I understand it, tons of data will be put into a supercomputer and this will somehow lead to a global understanding of how the brain works, but to simulate the brain, or a part of the brain, one has to start with some hypothesis about how it works. Until we at least have some well-grounded theoretical framework, building a huge simulation is putting the cart before the horse”. The goal of the RIDC NeuroMat is the development of this theoretical framework. This pioneer initiative by FAPESP’s RIDC NeuroMat puts São Paulo at the forefront of worldwide research in neuroscience.

The RIDC NeuroMat is a center of mathematics whose mission is to develop the new mathematics needed to construct a Theory of the Brain accounting for the experimental data gathered by neuroscience research. The long-term objective is to understand and explain complex neuroscientific phenomena, with focus on learning and memory. Neuromathematics is envisioned, at this time, as conjoining probability theory, statistics, and neuroscience. This requires the definition of a full new class of mathematical models to describe and explain in a parsimonious way the different scales of neural activity, their relationship and behavioral consequences. The construction of these models occurs together with the development of novel statistical and computational methods.

NeuroMat has fostered and leads a worldwide network (Brazil, Argentina, China, Finland, France, Germany, Italy, Uruguay, and USA) of over fifty mathematicians, neuroscientists, computational scientists, applied statisticians and clinicians. Since its inception in 2013, the NeuroMat team produced 261 articles, which have been cited 1,236 times.

The international and multidisciplinary research network built by NeuroMat was made possible within the long-term support framework provided by FAPESP’s conception of the RIDCs, aiming at cutting-edge knowledge in scientific research, innovation and dissemination.

A main scientific achievement was the introduction by the NeuroMat team of a new class of stochastic processes aimed at a realistic description of nets of spiking neurons. These processes are systems with infinitely many interacting chains with memory of variable length. Since their introduction, these stochastic processes have become part of the research agenda of several centers in the world.

Our contributions to the investigation of this new class of stochastic processes include:

the identification of mathematical conditions assuring the existence of the processes together with the design of a perfect simulation algorithm for their numerical implementation;

results on the hydrodynamical limit of processes belonging to the class. This is an important step to relate different scales of description of the system, from the microscopic level, modelling systems of spiking neurons, to the mesoscopic and macroscopic levels, describing EEG and fMRI data;

existence of phase transition for a specific instantiation of these models with leakage, setting a new framework for the rigorous investigation of spontaneous transitions of brain activity states, e.g. healthy to seizure-like activity. This is the first phase transition result rigorously proved for a mathematical model describing a system of interacting spiking neurons;

introduction of a novel estimator of the interaction graph for models in this class and the proof of its strong consistency, not requiring the usual assumptions of stationarity and uniqueness of the invariant measure. This contribution addresses an important issue in contemporary neurobiology, namely the question of how to infer neural interactions from the activity of an ensemble of neurons.

A second major achievement is the introduction of a new mathematical approach to address the classical conjecture that the brain retrieves statistical regularities from sequences of stimuli. This approach is based on a new class of stochastic processes, namely sequences of random objects driven by chains with memory of variable length. These processes appear as good candidates to model the relationship between sequences of stimuli and sequences of suitably parsed brain signals and behavioral states registered while exposed to stimuli.

This framework offers a new way to model structural learning and memory in the brain, including the following promising directions of research:

It provides an effective way to identify brain sensitivity and reaction to sequences of stimuli which goes much beyond the possibilities offered by current averaging-based methods;

As a consequence, it allows the introduction of a entire new class of experimental protocols in which physiological or behavioral data are recorded while a volunteer is exposed to sequences of stimuli generated by a stochastic chain with memory of variable length;

This approach offers promising perspectives in clinical neuroscience by identifying different signatures in response to structured sequences of stimuli in neurological disorders;

From a purely statistical point of view, sequences of random objects driven by chains with memory of variable length constitute an innovative tool in functional data analysis and high dimension statistics.

Innovation and Technology Transfer

The innovation mission of the RIDC NeuroMat is to develop tools and applications based on the new conceptual framework to understand the brain.

A spin-off of the new class of experimental protocols devised by NeuroMat is the Goalkeeper Game, an open-source, online game with desktop and mobile device versions, which provides an efficient tool for massive data collection. The game is freely available at: game.numec.prp.usp.br and also at Apple Store and Google Play.

The Goalkeeper Game has potential to be used as an early assessment and rehabilitation tool in neurology, and the NeuroMat technology transfer team is currently testing its applicability in two current clinical development fronts: Parkinson’s disease and brachial plexus injuries. Preliminary studies showed that the game has higher predictive power than the Montreal Cognitive Assessment (MoCA) test for gait performance in people with Parkinson’s disease.

NeuroMat developed the Neuroscience Experiments System (NES), a free, online opensource user-friendly computational platform to assist researchers in data and metadata collection and experiments management. Up to now NES has supported 22 experiments, managing data of around 500 subjects.

Recently, NeuroMat launched the NeuroMat Open Database (https://neuromatdb.numec.prp.usp.br). This is a repository of data and metadata collected within NeuroMat providing free online access to the stored data.

Our group has pioneered the use of word graph analysis for computational phenotyping in psychiatry, neurology and education. Word graphs provide a fast and low-cost tool to quantify psychopathological symptoms previously accessible only through qualitative examination of specialists.

Dissemination

NeuroMat’s activities in science dissemination use innovative means to transform scientific culture, overcoming artificial field boundaries and contributing to foment an integrated and genuinely multidisciplinary approach to the study of the brain.

NeuroMat has become a global player in digital dissemination science. It is the world leading institutional producer of mathematics content on Wikipedia and the pioneer of the Wikipedia Year of Science in Latin America.

Content on Wikipedia produced by or with the support from the NeuroMat dissemination team has been viewed by 22 million people since 2014. In the same period, 14.3 million words were added on Wikipedia in the context of the NeuroMat Wikipedia Initiative.

NeuroMat has contributed 9,911 media files to the Wikimedia Commons, the repository of images and videos that feeds Wikipedia. This content was viewed 10.4 million times in August 2018 alone.

NeuroMat has established partnerships with museums to share their collections on the internet, particularly the University of São Paulo Museu do Ipiranga, Museu de Anatomia Veterinária and Matemateca. This has been featured as a key activity of preserving cultural knowledge, especially in the context of the fire at the Museu Nacional, in Rio de Janeiro. NeuroMat’s line of action with museum has also led to creating a special exhibition on brain biology at the Museu de Anatomia Veterinária (30,000 visitors every year) and to devising a project of the Statistician Brain exhibition at USP’s Parque CienTec.

Fostering a new generation of researchers

NeuroMat is strongly committed to training young researchers. The young scientists formed at the center come from different scientific backgrounds and countries. This diversity fosters a genuine multidisciplinary team and a research practice that is necessary for the development of contemporary neuroscience.

NeuroMat has become the organizer of the Latin American School on Computational Neuroscience (LASCON), which is the first and most important school of computational neuroscience in Latin America.

Fifty-five young researchers have been trained at NeuroMat since its inception, in 2013. The team of young researchers the RIDC NeuroMat has trained includes: 10 technical training fellows, 13 postdoctoral researchers, 18 PhD candidates, 7 Master students and 7 scientific journalism fellows. These researchers have worked on probability theory, statistics, simulations, software development, neurobiology and dissemination.

Understanding how early humans developed their capacities of expression which led to emergence of the language which sets us apart from other species was the topic of an article published in the Frontiers in Psychology journal in February this year. Led by researcher Shigeru Miyagawa, a professor from the Massachusetts Institute of Technology (MIT), in the USA, with the participation of linguists Cora Lesure (MIT) and Vitor Augusto Nóbrega, from the School of Philosophy, Letters and Human Sciences (FFLCH) of USP, the study suggests cave paintings represent a modality of language expression.

The so-called rock art is one of the terms for the oldest known artistic representations, the oldest of which date back from the Upper Paleolithic (40,000 b.C.) and were drawn on rocky walls and ceilings of shelters or caves. According to scientists, the secret for understanding the leap taken by humans towards language might have started within those small spaces.
‘We take up the topic of cave art and archeoacoustics, particularly the discovery that cave art is often closely connected to the acoustic properties of the cave chambers in which it is found’ the researchers explain in the introduction of their article. For them, ‘early modern humans were able to detect the way sound reverberated in these chambers, and they painted artwork on surfaces that were acoustic “hot spots,” i.e., suitable for generating echoes’.

Based on that, linguists argue cave art is “a form of cross-modality information transfer, in which acoustic signals are transformed into symbolic visual representations”. That is, it is the first sign of “how the symbolic mind of early modern humans was taking shape into concrete, externalized language”.
Beyond the allegory and the cave

Prof saxx – Wikimedia Commons

A linguist graduated from USP, Nóbrega started his academic career studying how compound words, such as “glass cleaner”, “swordfish”, etc., were formed in different languages, and which the minimum requirements were for forming them in any language. In his doctoral studies, his focus shifted to how human beings managed to considerably expand their vocabulary, a field known as Biolinguistics. The contact with Professor Miyagawa started from this work.

As he tried to understand how we develop what he called lexical competence — the knowledge and capacity to use the vocabulary to form sentences in a language — the linguist went deeper on studying the origins of language in an attempt to uncover how it developed in the context of evolution, a mystery yet to be solved by scientists, and which has intrigued researchers across the world.

“There are reasons to believe the cognitive underpinnings for the development of a symbolic consciousness were available at the time of the emergence of the Homo sapiens around 200,000 years ago”, he says as he emphasizes recent discoveries suggest the Neanderthals — an extinct human species — also possessed symbolic consciousness.

Archeoacoustics

“Our starting point is a hypothesis defined in several works on archeoacoustics, which suggest the location and subject matter of cave paintings are intimately related to the acoustic properties of the environment in which they were made”, he explains, and gives as examples hoofed animals, such as bulls or bison, which generally are drawn in chambers whose acoustic reverberations sound like hoof beats. It is not a coincidence there are cave walls which would have been perfectly suited for painting, but which were ignored because of the acoustic properties of the cave chambers. Generally speaking, early humans painted not only what they saw, but also what they heard.

“Archeoacoustics is not the only hypothesis; and not all paintings features acoustic properties like this one. But there is a relation between the location and the subject matter with significant statistical outcomes”, argues Vitor as he stresses the research suggests cave artists already made use of a reasoning which “stemmed from symbolic consciousness”.

“Based on that relation, we suggest the mechanisms these cave representations seem to display are a parallel to what allowed us to develop human language through speech and signals”, he sums up.

The same idea among different species

Coincidently, at the same time his article was released, two other studies had an impact on the scientific community for they managed to prove cave paintings could be older than previously thought, dating about 60,000 years ago, when the Homo sapiens did not exist in Europe. That means the Neanderthals might have been the first artists. With that new information, scientists now need to think about how this competence sprang up at the same time in two different species.

Thomas T. / Wikimedia Commons

Even if cave art cannot be seen itself as language, Nóbrega says its production might suggest “the mechanisms underlying the production of painting run parallel to the production of language”. Then, we need to see them from a multi-sensory point of view, so we can identify correlations concerning how these paintings represented an advance which might have promoted human language.

Just like archeology might be viewd as a reconstruction — as archeologists dig for new evidence to either confirm or disprove historical hypotheses — “the study of language formation is also a reconstruction”, argues Nóbrega, as he highlights Linguistics is an “extremely interfaced” field in which one needs to pay close attention to discoveries being made in archeology, biology, psychology, among a diversity of other fields.

Despite that, “unfortunately, we will never have any direct evidence of what the first form of language used by the species was like”. However, we can examine the relation between archeological records, cave paintings, and the cognitive processes needed for them to come up. It is from this investigation “we can shed light on the timeline of human evolutionary development”, he remarks.

Click here to access the article Cross-Modality Information Transfer: A Hypothesis about the Relationship among Prehistoric Cave Paintings, Symbolic Thinking, and the Emergence of Language. For more information, email: vitor.augusto.nobrega@gmail.com

Bison in the Altamira Cave
Animals painted in the Lascaux Cave, one of the world’s most famous cave art sites – Animals drawn in the Chauvet Cave, generally considered the oldest cave paintings

Traditional treatments of industrial effluent, that is, the resulting liquid waste sent out from factories, are mainly based on removing pollutants, and then throwing them in water courses. The search for more sustainable alternatives than that one, which make use of technological advances is the focus of the work developed by Vitor Cano, a doctoral student at the School of Arts, Sciences and Humanities (EACH) of USP. His research aims to do more than just treat wastes; it seeks to obtain energy from them.

His work – partially conducted at Columbia University, in New York, USA – seeks to conceive and operate a bioelectrochemical system called microbial fuel cell (MFC) in international literature. It is essentially a bioreactor which contains bacteria capable of consuming organic matter as they breathe, but also of transferring the electrons generated in the process out of the cells. This way, it is possible to transfer those electrons to an electrode, thus generating an electric current.

“This a very recent and promising technology, as it allows for direct generation of electricity from organic waste, such as industrial wastewater. In other words, it is possible to treat industrial effluent and generate electricity, instead of spending energy”, explains the graduate student in Sustainability from the EACH, who has since 2017 been taking part in the research group coordinated by Professor Kartik Chandran at the Department of Environmental Engineering of the American university.

The problem with nitrogen

According to Vitor Cano, the research phase he has been conducting at Columbia University seeks to further enhance the possibilities of this technology. “I have been adapting the microbial fuel cell to use not just organic matter as fuel, but also the nitrogen present in wastewater. This way, we reduce the organic load of industrial wastewater and allow for a new method for treatment in terms of nitrogen load, with the benefit of generating renewable energy.”

Vitor Cano / EACH

Thus, in addition to being a promising technology for wastewater treatment which protects the quality of surface and groundwater, the process will also allow for treating wastewater with high nitrogen load, such as landfill leachates and industrial and agro-industrial wastewater. The added benefit – not to be downplayed – is the resulting generation of energy.

The researcher points out today all known processes for treating or recovering nitrogen exact a considerable energy cost, and because of that he studies the application of an innovative prototype of microbial fuel cell (MFC), conceived at the sanitation laboratory at EACH from low-cost material, for generating energy by using organic matter and nitrogen as fuel. “I practically brought my whole experiment with me, which included bioreactors and an electronic system for online monitoring. Due to the complexity of the experiment, setting it up in a new environment was a great challenge for me”, he stresses. The student is advised by Professor Marcelo Antunes Nolasco, and takes part in the Group for Study and Research in Water, Sanitation and Sustainability, coordinated by the same professor at EACH. The building of the project bioreactors relied on great technical support from expert Kelliton Francisco, who works in the research group headed by professor Nolasco.

The preliminary results obtained in Brazil have demonstrated the capacity of the system for treatment and generation of energy. The studies carried out in the United States are still in their very initial phase, but they are likely to confirm nitrogen can be used as fuel in MFC. “At the moment the MFC is undergoing an adaptation phase, with a continued increase of electric current, which might be related to the development of an electrogenic microbial community capable of using nitrogen as an energy source”, says the scientist.

Vitor Cano will come back to EACH to carry out the last experimental phase of the project, in which other bioelectrochemical processes of the microbial fuel cell will be explored. “I hope to expand the possibilities for applying the technology, making it more versatile and, therefore, viable in real scale for different contexts and objectives.”

The doctoral program is scheduled to be completed in July, 2019. After defending his dissertation, Cano intends to carry on his academic career, working on research projects seeking to develop studies related to sanitation and sustainability.

From the EACH Communication Department. For more information, e-mail imprensa-each@usp.brRecent and promising technology allows for direct generation of electricity from organic waste, such as industrial wastewater. In the image, an experiment set up in a laboratory at Columbia University, in New York

A study published in the Cancer Research journal from the American Association for Cancer Research reveals a possible therapeutic use of Zika virus, which raised world health authorities’ concern in 2015, when virus infection during pregnancy was linked to children being born with microcephaly. Now, Brazilian researchers from the Center for Human Genome and Stem Cell Studies have shown for the first time in animals the deleterious effect from injecting low concentrations of purified virus preparations into human embryonal brain tumors implanted in immunosuppressed mice. The article is titled Zika virus selectively kills aggressive human embryonal CNS tumor cells in vitro and in vivo.

The studies were carried out by using mainly human cell lineages derived from two types of central nervous system (CNS) embryonal tumors: medulloblastoma and atypical teratoid rhabdoid tumor (AT/RT). They are tumors affecting mainly children under 5.

“CNS tumors are solid tumors occurring mainly in children and teenagers”, explains Oswaldo Keith Okamoto, a study co-lead author. “The peak of incidence for medulloblastoma occurs among children aged 4-5. A higher incidence of AT/RT has been observed in younger children up to 2 years old.”

Tumor regression was observed in 20 of 29 animals treated with Zika virus in the study. Complete remission — total tumor clearance — twas observed in seven of them (five with AT/RT and two with medulloblastoma). In some cases, the virus has also proven effective against metastases, as it either eliminated the secondary tumor or inhibited its growth.

Mayana Zatz / IB

Mayana Zatz, a coordinator from the Center and one of the co-lead authors, does not hesitate to call the results “spectacular”. The next step is to find partners for what is called in biomedical terms Phase 1 testing, not on animals any longer, but on people; and in this case, mainly on small children. That is one of the reasons why experienced Mayana is glowing with enthusiasm, which she tries to tone down as she talks about the research she has promoted.”We are going to have to slow our anxiety down and not put the chart before the horse. It’s very important to start with two or three patients, and if it works, subsequently include a larger number.”

For that, they will need larger amounts of purified virus, produced according to good cultivation practices required for testing in humans. This phase has been undertaken together with Butantan Institute, which has already provided the viruses and cooperated with the study. From then on, they will be able to design a protocol for application in patients.
Carolini Kaid, a doctoral student from the Center for Human Genome Studies, and whose advisor is Oswaldo Okamoto, is the first author of the study. She was especially in charge of dealing with the mice: she performed the surgeries for implanting tumors, injected Zika virus into them, and then followed up on the evolution.

Ten in safety

Ensuring the virus is safe is crucial for applying study findings to clinical practice. As regards that, the article results are promising. Concentrations of one viral particle per ten cells were sufficient to infect and kill cells derived from AT/RT and medulloblastoma tumors. Also, the virus has shown a high specificity for this type of cells.

“The virus did not infect tumor cells indiscriminately”, explains Okamoto. “It is very specific for tumor cells of the nervous system.”

Besides that, it did not infect already differentiated neurons, which is a very advantageous behavior if repeated in human with brain tumor.

Researchers also tested in vitro the functionality of viruses formed in tumor cells after infection. The results have shown these new viral particles are defective, which would prevent the virus from spreading uncontrollably throughout the patient’s body after antitumor treatment.

During the outbreak in 2015, hundreds of thousands of people were infected. Despite that, most patients, children and adults, remained asymptomatic. Only a small percentage of infected people developed serious conditions, such as Guillain-Barré syndrome or encephalitis. Such observations are very important when assessing the risks and safety of a new treatment.

“The outlook is quite positive”, says Okamoto. “But we have a path to tread before we can warrant taking it into clinical trial.”

The experiments

The study outcomes show Zika virus can infect and kill CNS embryonal tumors with great efficacy and specificity, both in in vitro and in mouse models. The virus was tested in cells derived from prostate, breast, and colon tumors; besides three lineages of CNS embryonal tumors, a commercial one of medulloblastoma (DAOY) and two generated by the researchers themselves, one of medulloblastoma (USP-13), and another one of AT/RT (USP-7). Concentrations of two viral particles for each tumor cell killed most CNS tumor cells, but they were little effective on other lineages. However, even lower viral amounts — of one viral particle for each ten cells — inhibited the growth of CNS tumor cells.

Virus specificity was also assessed in three-dimensional cultures, in which the effect was even more evident, as the Zika virus preference for stem cells from CNS embryonal tumors was shown to be greater than for neural progenitor cells. In in vivo experiments, CNS embryonal tumors of human origin were grafted into mice. When these animals were treated with Zika virus, most tumors remitted, and metastases shrank. Researchers were also able to relate the Zika virus effects to the Wnt molecular pathway, a pathway already described as important in the development of AT/RT and medulloblastoma.

Virus did not infect tumor cells indiscriminately in preclinical study on mice, displaying great specificity to the nervous system, or already differentiated neurons. That is a very advantageous behavior if it is proved it can be repeated in humans bearing brain tumors. In the image a MRI scan shows a medulloblastoma in a human patient, a tumor which usually occurs in children aged 4-5